CFAR Clinical Research Pilot Project, Tuofu, Zhu, MD
Extensive studies indicate that host genetic variability affects the risk for HIV-1 infection and disease progression. This variability comes from polymorphisms in genes such as C-C chemokine receptor 5 (CCR5)-Δ32, CCR5 promoter polymorphisms, CCR2-64I, SDF1-3’A, and RANTES -28G / -403A. Among these, only CCR5-Δ32 has clearly shown to be associated with the resistance to HIV-1 infection. We have screened our cohorts of Exposed Seronegative (ES) , HIV-1 infected, HIV-1 negative, and long term non-progressors for these polymorphisms as well as the coding regions of CCR5, CXCR4, CCR1, CCR2b, CCR3 and CCR4. As reported by other groups, we observed that only homozygous CCR5-Δ32 is convincingly associated with the ressistance to HIV-1 infection in our ES. However, homozygous CCR5-Δ32 is found only in 3% (2/60) in our ES (same in other reported Caucasian ES cohorts) and 1% of general Caucasian population, but not in Africans and Asians. These results indicate other human genetic mutations that may affect HIV-1 infection.
In the past years, we have screened for new host gene polymorphisms that may affect HIV transmission and/or diseases progression. We have identified new genetic polymorphisms that affect HIV-1 transmission. We plan to extend these studies by: (1) conducting further study in larger populations worldwide; (2) searching for new human genes; (3) conducting function studies on newly identified mutants and develop theraputic stategies for HIV-1 infection.
